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1.
Mem Inst Oswaldo Cruz ; 116: e200572, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33886871

RESUMEN

BACKGROUND: The genetic heterogeneity of Leishmania parasites is a major factor responsible for the wide variety of Leishmania-associated manifestations. Consequently, understanding the genetic make-up of Leishmania species using suitable molecular markers is an important component of realising local and regional scale disease risk. The cytochrome b (cytb) is frequently used to type New World Leishmania species. However, its potential to discriminate Leishmania species and variants requires further evaluation. OBJECTIVES: To explore the capacity of cytb gene to identify New World Leishmania species and variants and to develop an approach able to type local Leishmania species and variants. METHODS: We retrieved 360 partial and complete Leishmania cytb gene sequences publicly available in GenBank database to study all single nucleotide polymorphisms (SNPs) across the cytb gene that differentiate New World Leishmania species. This information was used to develop an approach based upon the polymorphisms found in a DNA segment of 948bp. We also compared the typing results found with this technique with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) profiling obtained using HSP70 gene as target. One hundred Panamanian isolates were used to both typed Leishmania species and assess local genetic variability. FINDINGS: We found complete agreement between our cytb approach and the PCR-RFLP profiling method based on HSP70 for Leishmania species identification. Ninety-two isolates were identified as L. panamensis, although other Viannia species were found circulating at a lower frequency. Three L. panamensis haplotypes were identified in Panamanian provinces. We also provide an initial report of L. guyanensis haplotypes circulating in Panama. MAIN CONCLUSIONS: Cytb gene sequence encompasses key main SNPs that aid to identify Leishmania species. The cytb approach developed with this information was able to identify and assess genetic variability of local Leishmania species found in this study.


Asunto(s)
Leishmania , Leishmaniasis Cutánea , Citocromos b/genética , ADN Protozoario/genética , Humanos , Leishmania/genética , Panamá , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción
2.
BMC Infect Dis ; 21(1): 369, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33874901

RESUMEN

BACKGROUND: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1ß), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4-5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL. METHODS: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls. RESULTS: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r = - 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. CONCLUSIONS: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.


Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Linfocitos T CD4-Positivos/citología , Inmunoglobulina G/sangre , Leishmania/inmunología , Leishmaniasis Visceral/patología , Adulto , Anfotericina B/uso terapéutico , Brasil , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Ácido Desoxicólico/uso terapéutico , Combinación de Medicamentos , Femenino , Infecciones por VIH/complicaciones , Humanos , Interleucina-6/sangre , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/inmunología , Masculino , Persona de Mediana Edad , Recurrencia
3.
Mem Inst Oswaldo Cruz ; 116: e200571, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33681890

RESUMEN

Leishmania infantum chagasi is the causative agent and Lutzomyia longipalpis is the main vector of visceral leishmaniasis in the Americas. We investigated the expression of Leishmania genes within L. longipalpis after artificial infection. mRNAs from genes involved in sugar and amino acid metabolism were upregulated at times of high parasite proliferation inside the insect. mRNAs from genes involved in metacyclogenesis had higher expression in late stages of infection. Other modulated genes of interest were involved in immunomodulation, purine salvage pathway and protein recycling. These data reveal aspects of the adaptation of the parasite to the microenvironment of the vector gut and reflect the preparation for infection in the vertebrate.


Asunto(s)
Insectos Vectores/parasitología , Leishmania infantum/genética , Leishmania/aislamiento & purificación , Leishmaniasis Visceral/transmisión , Psychodidae/parasitología , Animales , Brasil , Expresión Génica , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/parasitología , Estadios del Ciclo de Vida , Psychodidae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
4.
Rev Soc Bras Med Trop ; 54: e0748-2020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33759927

RESUMEN

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania spp. The recurrence of the disease occurs, in general, in patients with decreased or loss of T-cell function, whether due to the use of corticosteroids, immunosuppressive disease, or another cause. In some cases, splenectomy may be a therapeutic option. However, the effectiveness of splenectomy is not well defined. This report describes the evolution of a pediatric patient with seven recurrences of VL, who relapsed post-surgery after drug therapy and splenectomy.


Asunto(s)
Leishmania , Leishmaniasis Visceral , Niño , Humanos , Leishmaniasis Visceral/tratamiento farmacológico , Recurrencia , Esplenectomía
5.
Rev Soc Bras Med Trop ; 54: e0772-2020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33759929

RESUMEN

Leishmaniasis is a tropical infectious disease caused by Leishmania spp. protozoa and is transmitted by insects from the Phlebotominae subfamily. It can manifest as cutaneous leishmaniasis, a painless ulcer that can develop into a more serious systemic affliction as the protozoa spreads lymphatically or hematogenously, depending on the host's immunity. In this case series, the authors present a rare form of genital mucocutaneous leishmaniasis, with consideration of epidemiologic characteristics, clinical presentation, differential diagnosis, and treatments offered.


Asunto(s)
Leishmania , Leishmaniasis Cutánea , Leishmaniasis Mucocutánea , Animales , Diagnóstico Diferencial , Genitales , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Mucocutánea/diagnóstico , Úlcera
6.
Molecules ; 26(4)2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33671969

RESUMEN

The fractionation of an ethanol extract of the bark of Trichilia adolfi yielded four novel limonoids (trichilinones A-D, 1-4), with five fused rings and related to the hortiolide-type limonoids. Starting with an ε-lactone, which is α,ß-unsaturated in trichilinones A and D (1 and 4), attached to a tetrahydrofuran ring that is connected to an unusual bicyclo [5.1.0] hexane system, joined with a cyclopentanone with a 3-furanyl substituent [(2-oxo)-furan-(5H)-3-yl in trichilinone D (4)], the four compounds isolated display a new 7/5/3/5/5 limonoid ring system. Their structures were established based on extensive analysis of NMR spectroscopic data. As the crude extract possessed anti-leishmanial properties, the compounds were assayed for cytotoxic and anti-parasitic activities in vitro in murine macrophages cells (Raw 264.7) and leishmania promastigotes (L. amazoniensis and L. braziliensis), respectively. The compounds showed moderate cytotoxicity (approximately 70 µg/mL), but are not responsible for the leishmanicidal effect of the extract.


Asunto(s)
Ciclopropanos/análisis , Limoninas/análisis , Meliaceae/química , Animales , Espectroscopía de Resonancia Magnética con Carbono-13 , Ciclopropanos/química , Ciclopropanos/farmacología , Leishmania/efectos de los fármacos , Limoninas/química , Limoninas/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Ratones , Espectroscopía de Protones por Resonancia Magnética , Células RAW 264.7
7.
Mem Inst Oswaldo Cruz ; 116: e200634, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33787768

RESUMEN

The availability of Trypanosomatid genomic data in public databases has opened myriad experimental possibilities that have contributed to a more comprehensive understanding of the biology of these parasites and their interactions with hosts. In this review, after brief remarks on the history of the Trypanosoma cruzi and Leishmania genome initiatives, we present an overview of the relevant contributions of genomics, transcriptomics and functional genomics, discussing the primary obstacles, challenges, relevant achievements and future perspectives of these technologies.


Asunto(s)
Genoma de Protozoos/genética , Leishmania/genética , Trypanosoma cruzi/genética , Biología Computacional , Genómica
8.
Artículo en Inglés | MEDLINE | ID: mdl-33503150

RESUMEN

American Tegumentary Leishmaniasis (ATL) is endemic in the municipality of Montes Claros, Minas Gerais State. The use of geotechnology such as spatial statistics and remote sensing has contributed to a better understanding of the eco-epidemiology of diseases, and consequently a better definition of control strategies. This study aimed to analyze the spatial distribution of probable sites of cases of ATL infection (2007-2011) in the municipality of Montes Claros and to identify related socio-environmental factors. Data on ATL cases notification were obtained from the Municipal Health Department of Montes Claros. The annual incidence of ATL in the municipality was calculated and the probable sites of infection were georeferenced. Crude Rate and the Local Empirical Bayesian Rate were calculated with census sectors considered as the unit of analysis. The Normalized Difference Vegetation Index (NDVI) was calculated from LANDSAT 5 TM images. The spatial association between the crude rate of ATL and the NDVI of the census tracts was evaluated using the Local Bivariate of Moran I. The socio-environmental aspects of household structures were assessed based on a structured questionnaire. The incidence of ATL in the evaluated period ranged from 6.2 to 16.6 cases/100,000 inhabitants. The highest rates of ATL occurrence were found in the census sectors located in the rural area and in the peripheral census sectors in the city. Through the Empirical Bayes Smoothed Rate map, it was found that in the peripheral areas of the city, the rates of ATL occurrence were lower than in the rural area and their values decreased as they approach the city center. Local Bivariate of Moran I showed a positive correlation between NDVI and crude ATL rates, with significant high-high clusters observed in the rural area and in the census sectors in the Western peripheral area of the city that have experienced an urban expansion concomitant to the period investigated. In most homes of people affected by the disease, there were domestic animals and organic matter in the peridomicile. In addition, a high percentage of individuals affected by ATL reported the presence of rodents circulating near their homes. In conclusion, it is possible that the disorderly expansion process in the city of Montes Claros favored the establishment of the ATL periurban and urban transmission cycle. These regions deserve special attention from health surveillance to combat this zoonosis.


Asunto(s)
Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/epidemiología , Animales , Teorema de Bayes , Brasil/epidemiología , Ciudades/epidemiología , Salud Ambiental , Incidencia , Leishmania/genética , Factores Socioeconómicos , Análisis Espacial
9.
Mediators Inflamm ; 2021: 6699560, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33505216

RESUMEN

Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.


Asunto(s)
Antiinflamatorios/farmacocinética , Ácido Glicirretínico/farmacocinética , Ácido Glicirrínico/farmacocinética , Factores Inmunológicos/farmacocinética , Animales , Citocinas/metabolismo , Medicamentos Herbarios Chinos/farmacocinética , Glycyrrhiza/química , Humanos , Inflamación , Interferones/metabolismo , Interleucinas/metabolismo , Leishmania/metabolismo , Sistema de Señalización de MAP Quinasas , Macrófagos/metabolismo , Macrófagos/parasitología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Prostaglandinas/metabolismo , ARN Mensajero/metabolismo , Células TH1/citología , Receptores Toll-Like/metabolismo
10.
Parasitol Res ; 120(3): 785-796, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33409640

RESUMEN

Leishmania spp. and Trypanosoma cruzi are parasites belonging to the Trypanosomatidae family and the causative agents for two very important neglected tropical diseases (NTDs), namely leishmaniasis and trypanosomiasis, respectively. Together, they affect millions of people worldwide and the number of cases is constantly rising; thus, further effort on identifying and developing non-toxic, affordable and effective new drug is urgently needed to overcome this alarming situation. Exploring natural products from fungal and bacterial origin remains hitherto a valuable approach to find new hits and candidates for the development of new drugs against these protozoal human infections. Endophytes, which are microorganisms (fungal and bacterial) inhabiting plant tissues, represent a promising source, as they hold potential to produce a high number of distinct chemical scaffolds. These structurally diverse natural products have previously been successfully tested against a wide range of pathogenic microorganisms. The present review provides an update of endophytic compounds exerting anti-trypanosomal and anti-leishmanial effects and their predicted pharmacokinetic properties.


Asunto(s)
Antiprotozoarios/farmacología , Bacterias/química , Productos Biológicos/farmacología , Endófitos/química , Hongos/química , Leishmania/efectos de los fármacos , Trypanosoma cruzi/efectos de los fármacos , Animales , Humanos , Leishmania/fisiología , Leishmaniasis/tratamiento farmacológico , Leishmaniasis/parasitología , Plantas/microbiología , Trypanosoma cruzi/fisiología , Tripanosomiasis/tratamiento farmacológico , Tripanosomiasis/parasitología
11.
Acta Trop ; 215: 105806, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33385363

RESUMEN

Treatment of tegumentary leishmaniasis in Brazil is limited to pentavalent antimonial, amphotericin B and pentamidine. These drugs, administered parenterally, cause several side effects and have a varied clinical response, depending on the species of Leishmania. Urgent expansion of the therapeutic arsenal against the disease is therefore necessary. Paromomycin is an aminoglycoside antibiotic that has already been approved for the treatment of visceral leishmaniasis in Southeast Asia. Here, we provide an in vitro evaluation of the activity of paromomycin in fifteen clinical isolates from patients with tegumentary leishmaniasis at a reference center for the treatment of the disease. Furthermore, the in vitro susceptibility to this drug in reference strains of Leishmania species that are endemic in Brazil has also been evaluated. Among the clinical isolates, nine were typed as Leishmania (Viannia) braziliensis, five as L. (Leishmania) amazonensis and one as L. (V.) guyanensis. Although never exposed to paromomycin, we found variable susceptibility among these isolates and reference strains in promastigotes and intracellular amastigotes, with the drug being more active in the amastigote form of the parasite. This study provides a preclinical dataset that is useful for the evaluation of paromomycin in the treatment of tegumentary leishmaniasis caused by species that are endemic in Brazil.


Asunto(s)
Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Leishmaniasis Cutánea/parasitología , Paromomicina/farmacología , Animales , Humanos , Leishmaniasis Cutánea/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C
12.
Chem Biol Interact ; 336: 109389, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33484715

RESUMEN

Leishmaniases are infectious diseases caused by protozoa of the genus Leishmania, that may have different clinical manifestations. First line drugs used in the treatment of leishmaniosis are high costly, and are very aggressive requiring medical monitoring. Thus new therapeutic alternatives are needed and, in this context, natural products have been considered as a source of new antileishmania agents. Riparins are alkamides found in the unripe fruits of Aniba riparia. Several biological activities are described for this group of compounds, such as antimicrobial and antiparasitic potential. The objective of this work was to evaluate the anti-leishmania activity riparin E (Rip-E) in vitro, against promastigotes and internalized amastigotes of Leishmania amazonensis. Rip-E was able to inhibit promastigote cell growth (IC50 4.7 µg/ml) and to reduce the percentage of macrophages infected with amastigotes, reducing its infectivity (survival index) (IC50 1.3 µg/ml). The cytotoxicity against BALB/c murine macrophages was also assessed (CC50 50.6 µg/ml) and the selectivity index was 38.9. Rip-E also demonstrated immunomodulatory activity, evidenced by the increase of the phagocytic capacity and lysosomal activity. However, Rip-E did not affect directly the production of nitric oxide. These results suggest that Rip-E has antileishmania potential, by both its direct inhibitory effect and its ability to activate macrophages.


Asunto(s)
Antiprotozoarios/farmacología , Inmunomodulación , Leishmania/efectos de los fármacos , Macrófagos/efectos de los fármacos , Animales , Antiprotozoarios/síntesis química , Antiprotozoarios/química , Proliferación Celular/efectos de los fármacos , Femenino , Leishmania/inmunología , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Pruebas de Sensibilidad Parasitaria
13.
Adv Protein Chem Struct Biol ; 123: 73-93, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33485489

RESUMEN

Autophagy is a self-destructing mechanism of cell via lysosomal degradation, which helps to degrade/destroy hazardous substances, proteins, degenerating organelles and recycling nutrients. It plays an important role is cellular homeostasis and regulates internal environment of cell, moreover, when needed causes non-apoptotic programmed death of cell. Autophagy has been observed as one of the major factors in parasite clearance in leishmaniasis. Being an intra-cellular pathogen, the cell mediated response is the only alternative for adaptive immunity against Leishmania in host. Pro-inflammatory cytokines IL12 and TNFα generate Th2 response which helps in active phagocytosis of parasite whereas an anti-inflammatory cytokine like IL10 mediate parasite promotion by blocking autophagic pathways and inhibiting phagocytic actions. In the present chapter, through systems biology approach, we are trying to decipher the role of pro-inflammatory and anti-inflammatory cytokine in autophagy during leishmanial infection. TLR2/6 mediated signaling stimulated by LPG produces many pro-inflammatory cytokines like IL12, TNFα and IL6 etc. Among them TNFα, causes the activation of PI3P through a series of events, which results in activation of autophagic machinery, whereas, IL10 through ATG9 and mTOR activation, inhibits autophagy. The mathematical modeling of these pathways shows that, ATG9-PI3P act as a negative feedback loop in autophagic machinery of leishmaniasis.


Asunto(s)
Proteínas Relacionadas con la Autofagia/inmunología , Autofagia/inmunología , Homeostasis/inmunología , Leishmania/inmunología , Leishmaniasis/inmunología , Modelos Inmunológicos , Células Th2/inmunología , Citocinas/inmunología , Humanos
14.
Biochim Biophys Acta Biomembr ; 1863(1): 183473, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-32937102

RESUMEN

Two ß-carboline compounds, 8i and 6d, demonstrated in vitro antileishmanial activity against Leishmania (L.) amazonensis promastigotes similar to that of miltefosine (MIL). Estimates of the membrane-water partition coefficient (KM/W) and the compound concentrations in the membrane (cm50) and aqueous phase (cw50) for half maximal inhibitory concentration were made. Whereas these biophysical parameters for 6d were not significantly different from those reported for MIL, 8i showed lower affinity for the parasite membrane (lower KM/W) and a lower concentration of the compound in the membrane required to inhibit the growth of the parasite (lower cm50). A 2-hour treatment of Leishmania promastigotes with the compounds 8i and 6d caused membrane rigidity in a concentration-dependent manner, as demonstrated by the electron paramagnetic resonance (EPR) technique and spin label method. This increased rigidity of the membrane was interpreted to be associated with the occurrence of cross-linking of oxidized cytoplasmic proteins to the parasite membrane skeleton. Importantly, the two ß-carboline-oxazoline derivatives showed low hemolytic action, both in experiments with isolated red blood cells or with whole blood, denoting their great Leishmania/erythrocyte selectivity index. Using electron microscopy, changes in the membrane of both the amastigote and promastigote form of the parasite were confirmed, and it was demonstrated that compounds 8i and 6d decreased the number of amastigotes in infected murine macrophages. Furthermore, 8i and 6d were more toxic to the protozoa than to J774A.1 macrophages, with treated promastigotes exhibiting a decrease in cell volume, mitochondrial membrane potential depolarization, accumulation of lipid bodies, increased ROS production and changes in the cell cycle.


Asunto(s)
Antiprotozoarios/farmacología , Carbolinas/farmacología , Membrana Celular/metabolismo , Leishmania/metabolismo , Animales , Antiprotozoarios/química , Carbolinas/química , Humanos , Ratones , Proteínas Protozoarias/metabolismo
15.
Rev Soc Bras Med Trop ; 53: e20200255, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33331607

RESUMEN

INTRODUCTION: In the Belém Metropolitan Region (BMR), Pará State, Brazil, American cutaneous leishmaniasis (ACL) is endemic; however, very little is known regarding its causative agents. Therefore, we used our standard diagnostic approach combined with an RNA polymerase II largest subunit (RNAPOIILS)-polymerase chain reaction (PCR) followed by analysis of restriction fragment length polymorphism (PCR-RFLP) to identify Leishmania spp. ACL agents in this region. METHODS: Thirty-two Leishmania spp. isolates from patients with ACL in the BMR during 1995-2018 were analyzed. Leishmania spp. DNA samples were amplified using the primers RPOR2/RPOF2, and the 615-bp PCR products were subjected to enzymatic digestion using TspRI and HgaI endonucleases. RESULTS: ACL etiological agents in the BMR comprised Leishmania (Viannia) lindenbergi (43.7%) followed by Leishmania (Viannia) lainsoni (34.4%), Leishmania (Leishmania) amazonensis (12.5%), and Leishmania (Viannia) braziliensis (9.4%). CONCLUSIONS: To our knowledge, the results of the study revealed for the first time that L. (V.) lindenbergi and L. (V.) lainsoni are the main ACL agents in BMR.


Asunto(s)
Leishmania braziliensis , Leishmania , Leishmaniasis Cutánea , Brasil/epidemiología , Humanos , Leishmania/genética , Leishmania braziliensis/genética , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/epidemiología , Polimorfismo de Longitud del Fragmento de Restricción , Estados Unidos
16.
PLoS Negl Trop Dis ; 14(12): e0008967, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33370303

RESUMEN

Phlebotomine sand flies employ an elaborate system of pheromone communication wherein males produce pheromones that attract other males to leks (thus acting as an aggregation pheromone) and females to the lekking males (sex pheromone). In addition, the type of pheromone produced varies among populations. Despite the numerous studies on sand fly chemical communication, little is known of their chemosensory genome. Chemoreceptors interact with chemicals in an organism's environment to elicit essential behaviors such as the identification of suitable mates and food sources. Thus, they play important roles during adaptation and speciation. Major chemoreceptor gene families, odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs) together detect and discriminate the chemical landscape. Here, we annotated the chemoreceptor repertoire in the genomes of Lutzomyia longipalpis and Phlebotomus papatasi, major phlebotomine vectors in the New World and Old World, respectively. Comparison with other sequenced Diptera revealed a large and unique expansion where over 80% of the ~140 ORs belong to a single, taxonomically restricted clade. We next conducted a comprehensive analysis of the chemoreceptors in 63 L. longipalpis individuals from four different locations in Brazil representing allopatric and sympatric populations and three sex-aggregation pheromone types (chemotypes). Population structure based on single nucleotide polymorphisms (SNPs) and gene copy number in the chemoreceptors corresponded with their putative chemotypes, and corroborate previous studies that identified multiple populations. Our work provides genomic insights into the underlying behavioral evolution of sexual communication in the L. longipalpis species complex in Brazil, and highlights the importance of accounting for the ongoing speciation in central and South American Lutzomyia that could have important implications for vectorial capacity.


Asunto(s)
Células Quimiorreceptoras/metabolismo , Proteínas de Insectos/genética , Leishmaniasis/prevención & control , Leishmaniasis/transmisión , Phlebotomus/parasitología , Atractivos Sexuales/química , Animales , Brasil , Femenino , Insectos Vectores/parasitología , Leishmania , Masculino , Phlebotomus/genética , Phlebotomus/fisiología , Polimorfismo de Nucleótido Simple/genética
17.
PLoS Negl Trop Dis ; 14(12): e0008963, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33382690

RESUMEN

Diagnosis of a first-time visceral leishmaniasis (VL) infection in Ethiopia is established by use of a rapid diagnostic test (RDT) detecting antibodies against rK39, direct agglutination test (DAT) and microscopy according to the national algorithm. The performance of individual tests and algorithm is variable and depends on several factors, one being HIV status. Limited data are available on the performance of tests in VL-HIV coinfected patients. Assessment of the performance of DAT (ITM-A), rK39 ELISA (Serion) and six RDT (Onsite Leishmania Ab CTK, Antigen ICT Xinjier, IT Leish Biorad, Kalazar Detect Inbios, rK39 IgG1 Coris, rk28 IgG1 Coris) for the diagnosis of VL was done on a panel of 91 stored serum and plasma samples of 'first-episode' suspected VL patients, with HIV coinfection (n = 51) and without (n = 40). A combined reference standard was used: either positive microscopy on tissue aspirates, or in case of negative microscopy, positive PCR results on the aspirate slide. Additionally, endemic healthy controls (n = 20), non-endemic controls (n = 10) and patients with confirmed malaria infection (n = 10) were tested for specificity evaluation. Sensitivities ranged from 69.2% for DAT (applied cut-off ≥ 1/3200) to 92.2% for the Onsite RDT, whereas specificities ranged from 20.0% for Kalazar Antigen ICT to 100% for IT Leish and rK39 IgG1. Sensitivities from all assays decreased upon stratification according to HIV status but was only significantly different for rK39 Serion ELISA (p-value 0.0084) and the Onsite RDT (p-value 0.0159). In conclusion, performance of commercially available assays for VL on samples from Northern-Ethiopian patients varied widely with a substantial decrease in sensitivity in the VL-HIV coinfected group. Clear guidelines on minimal performance criteria of individual tests and algorithms are needed, as well as which reference standard should be used to determine the performance.


Asunto(s)
Antígenos de Protozoos/inmunología , Infecciones por VIH/complicaciones , Leishmania/inmunología , Leishmaniasis Visceral/diagnóstico , Pruebas de Aglutinación , Pruebas Diagnósticas de Rutina , Ensayo de Inmunoadsorción Enzimática , Etiopía/epidemiología , Humanos , Leishmaniasis Visceral/parasitología , Estándares de Referencia
18.
Mem Inst Oswaldo Cruz ; 115: e200157, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206821

RESUMEN

BACKGROUND: In Acre state, Brazil, the dissemination of cutaneous leishmaniasis has increased in recent years, with limited knowledge of the potential Leishmania spp. vectors involved. OBJECTIVES: Here, data concerning the sandfly fauna of Brasiléia municipality, Leishmania DNA-detection rates and the identification of blood meal sources of insects captured in 2013-2015 are presented. METHODS: Parasite detection in female sandflies was performed individually by multiplex polymerase chain reaction (PCR) (Leishmania kDNA/sandfly cacophony-gene), with the identification of Leishmania spp. by hsp70-PCR and sequencing. The identification of blood gut-content from fed females was performed by cyt b-PCR and sequencing. FINDINGS: A total of 4,473 sandflies were captured. A subgroup of 864 non-blood-fed females evaluated for the presence of Leishmania DNA showed 2.9% positivity for Leishmania (Viannia) braziliensis and L. (V.) guyanensis. The identification of blood meal sources was performed in 96 blood-fed females, allowing the identification of 13 vertebrate species. In nine/96 fed females, DNA from L. (V.) shawi, L. (V.) guyanensis, L. (V.) braziliensis and Endotrypanum sp. was detected. MAIN CONCLUSIONS: In Brumptomyia sp. and Evandromyia termitophila, the first report of Leishmania DNA-detection is provided in Acre; Nyssomyia shawi is implicated as potential vector of L. (V.) braziliensis and L. (V.) guyanensis for the first time in Brazil.


Asunto(s)
ADN/análisis , Insectos Vectores/genética , Leishmania/genética , Psychodidae/parasitología , Animales , Brasil , ADN Protozoario/análisis , Femenino , Insectos Vectores/clasificación , Insectos Vectores/parasitología , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/transmisión , Reacción en Cadena de la Polimerasa , Psychodidae/clasificación
19.
Mem Inst Oswaldo Cruz ; 115: e200272, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206822

RESUMEN

BACKGROUND: Metformin (MET) is a hypoglycemic drug used for the treatment of diabetes, despite interference in host immunity against microorganisms. Cutaneous infection caused by pathogens such as Leishmania braziliensis (Lb), the agent responsible for cutaneous leishmaniasis (CL) in Brazil, represents an interesting model in which to evaluate the effects associated with MET. OBJECTIVE: To evaluate the modulatory effect of MET in Lb infection. MATERIAL AND METHODS: Experimental study of Lb infection and MET treatment in BALB/c mice and Raw 264.7 macrophages. FINDINGS: MET treatment interfered with lesion kinetics, increased parasite load and reduced macrophage proliferation. Low concentrations of MET in Lb culture allow for the maintenance of stationary parasite growth phase. Lb-infected cells treated with MET exhibited increased parasite load. While both MET and Lb infection alone promoted the production of intracellular reactive oxygen species (ROS), reduced levels of ROS were seen in MET-treated Lb-infected macrophages. MAIN CONCLUSION: Experimental treatment with MET interfered with the kinetics of cutaneous ulceration, increased Lb parasite load, altered ROS production and modulated cellular proliferation. Our experimental results indicate that MET interfere with the evolution of CL.


Asunto(s)
Leishmania/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Metformina/farmacología , Animales , Brasil , Leishmania braziliensis , Ratones , Ratones Endogámicos BALB C
20.
Artículo en Inglés | MEDLINE | ID: mdl-33027391

RESUMEN

Asymptomatic VL is a concern, considering the risk of transmission in highly endemic areas due to human-to-human transmission. The aim of this study was to report the sero-epidemiological prevalence in Bihar, India, a highly endemic area of VL, using the leishmanin skin test (LST) and the direct agglutination test (DAT). This was a cross-sectional study performed in Muzaffarpur, Bihar, India. Relatives of patients with VL were tested by LST and DAT. Other epidemiological data were evaluated and correlated with tests results. Forty individuals (either previous or current patients), and 109 household contacts were studied. There were 36% of male visceral leishmaniasis family members versus 17.57% of females visceral leishmaniasis family members, thus showing more males with symptomatic disease than females (p< 0.01). All visceral leishmaniasis cases had positive DAT tests, but only 37% of past cases were positive on the skin testing. Amongst healthy household contacts, 34% were DAT-positive, whilst 21% were LST-positive. The overall positivity for both assays combined was 44.8% and 23.8% were DAT-positive alone. The finding of high infection prevalence amongst asymptomatic individuals, and the estimation of those at greater risk for overt disease (DAT-positive alone) are important in the development of future disease control policies.


Asunto(s)
Leishmania/clasificación , Leishmania/aislamiento & purificación , Leishmaniasis Visceral/diagnóstico , Pruebas Cutáneas/métodos , Prueba de Coombs , Estudios Transversales , Femenino , Humanos , India , Leishmania/inmunología , Leishmaniasis Visceral/inmunología , Masculino
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